Filtering out the effect of large floods

Large floods should seemingly influence the depth and width of rivers. Phillips and Jerolmack, however, suggest that the self-organization of bedrock river channels blunts the impact of extreme rainfall events. River channel geometries from a wide range of course-grained rivers across the United States show that larger floods have very limited additional impact on channel geometry. River channel sculpting does increase as flood size increases, but the effect is most pronounced for moderate floods. This relationship may explain the long-term stability of rivers across shifts in climate.

Cosmic rays from a nearby supernova

Keith T. Smith

Supernova explosions produce unstable isotopes, spreading them through space in the form of cosmic rays. Binns et al. used NASA's Advanced Composition Explorer spacecraft to search for previously undetected traces of 60Fe in cosmic rays passing through the solar system. Seventeen years of observations detected just 15 60Fe nuclei—a small but statistically significant number. Because 60Fe is radioactive, with a half-life of 2.6 million years, these nuclei must have formed relatively recently in a nearby supernova. The most likely candidates are massive stars in the Scorpius-Centaurus association.

Climate filters dominant species

Sacha Vignieri

The transition between the Eocene and Oligocene periods was marked by distinct cooling. Because primate species are particularly susceptible to cold, this change in climate drove a retraction of primates globally. After this transition, anthropoid primates were dominant in Afro-Arabian regions, but little has been known about primate reestablishment in Asia. Ni et al. describe 10 previously unknown primates found in Yunnan Province in China that show that primates took a different path in Asia. Instead of anthropoids, strepsirrhine (lemur-like) primates were dominant. It is still unknown whether this difference was due to the environment or chance.

Growing patterned rectangular objects

Marc S. Lavine

The growth of patterned objects usually requires a template to aid the positioning of multiple materials. Qiu et al. used the seeded growth of a crystallizable block copolymer and a homopolymer to produce highly uniform rectangular structures (see the Perspective by Ballauff). Chemical etching, or dissolution, of uncross-linked regions of the rectangular structures produced perforated platelet micelles. The sequential addition of different blends and cross-linking/dissolution strategies allowed the formation of well-defined hollow rectangular micelles, which can be functionalized in a variety of ways.

Narrowing of the life expectancy gap

Gilbert Chin

In the United States, the rich can expect to enjoy better health and a longer life than the poor. Despite policies directed at improving the health of both the young and the poor, there is little evidence that this relationship has changed. Currie and Schwandt looked specifically at the life expectancy of present-day children and young adults, finding that mortality inequality has in fact declined over the past 25 years (see the Perspective by Bailey and Timpe).

Notch balances innate lymphoid cells

John F. Foley

In the gut, specialized cells either trigger inflammation or induce no immune response. Group 3 innate lymphoid cells (ILC3s), for example, balance tolerance to symbiotic gut microbes with inflammatory responses to invading pathogens. Chea et al. found that stimulation of the receptor Notch2 enhanced the production of a subset of ILC3s. Moreover, Viant et al. showed that Notch signaling was required to maintain these ILC3s, and its effects were opposed by the cytokine TGF-β. Thus, the proportions of ILC3 subsets depend on the balance between different signals in in the gut.

Sci. Signal.9, ra45 and ra46 (2016).

Neonatal Screening

A bile acid assay for timely diagnosis

Yevgeniya Nusinovich

Niemann-Pick type C (NPC) disease is a fatal neurological disorder caused by the deficiency of an enzyme involved in cholesterol storage. Although this disease was untreatable in the past, new therapeutics are now in clinical trials. The treatments are most likely to be effective if started as early as possible, before neurodegeneration has occurred. Jiang et al. identified three bile acids that are greatly increased in the blood of patients with NPC, as compared to healthy controls. One of these bile acids can be reliably measured in dried blood spots using mass spectrometry. The findings suggest this bile acid test as a possible addition to neonatal screening programs.

Sci. Transl. Med.8, 337a63 (2016).

Protein Design

Building new proteins from the old

Valda Vinson

Proteins are the workhorses of biology. Designing new, stable proteins with functions desirable in biotechnology or biomedicine remains challenging. Jacobs et al. developed a computational method called SEWING that designs proteins using pieces of existing structures (see the Perspective by Netzer and Fleishman). The new proteins can contain structural features such as pockets or grooves that are required for function. The solved structures of two designed proteins agreed well with the design models. The method allows rapid design of a diverse set of structures that will facilitate functional design.

Stay on the right track

Stella M. Hurtley

Cilia contain a well-ordered array of microtubule doublets along their length. A longstanding question in cilium structure and function is why the microtubule arrangement in cilia is so complex. Stepanek and Pigino developed a time-resolved correlative fluorescence and three-dimensional electron microscopy method to show that the doublets provide directionality to intraflagellar transport. One microtubule in the pair moves cargoes up to the ciliary tip. Meanwhile, the other microtubule moves cargoes back to the cell body. These results explain why the axoneme is built out of microtubule doublets and suggest a mechanistic picture of how the logistics of bidirectional intraflagellar transport are regulated.

The nongenetic roles of the nucleus

Laura M. Zahn

The eukaryotic cell nucleus provides a home for the genetic material and accessory proteins. As a physical entity, the nucleus also plays an important role in cell dynamics. Bustin and Misteli review the impacts that the nucleus can have as a nongenetic force. For example, compacted DNA and the nuclear membrane affect nuclear morphology, the cellular response to mechanical force, cell migration, and cell signaling. Chromatin is not only affected by physical forces in cells but participates in a crosstalk of signaling inside cells.

Deciphering the histone code

Guy Riddihough

Regulatory information is stored both in DNA sequences and in the chromatin proteins that package the genome. The covalent modification of histones plays a critical role in signaling whether a gene or genomic region should be active or inactive. Shema et al. used high-throughput single-molecule imaging to reveal the different combinations of modifications on millions of individual nucleosomes. Single-molecule DNA sequencing determined the exact location of these modified nucleosomes in the genome.

Faulty channels, not faulty synapses

Stella M. Hurtley

SHANK3 is a widely expressed scaffolding protein that is enriched in postsynaptic specializations. In mutant mice, SHANK3 mutations cause autism-like behavioral changes and exhibit alterations in synaptic transmission. Yi et al. produced human neurons lacking SHANK3 but not other genes that are also involved in the autism-like disease Phelan-McDermid syndrome. Instead of affecting synapses, SHANK3 mutations primarily caused a channelopathy, with the major phenotype consisting of a specific impairment of HCN channels. Chronic impairment of membrane currents through channelopathy could account for the phenotypes observed in Phelan-McDermid neurons, such as alterations in cognitive functions and the predisposition to epilepsy.

Rapid mixing to race past rearrangement

Jake Yeston

Chemistry relies on encounters between reactive partners. Sometimes one of the partners changes shape during the wait, spoiling the desired outcome. Kim et al. designed a microfluidic device to keep such botched encounters from happening. The device operates at low temperatures to keep individual reactants from isomerizing. It also achieves fast flow rates to maximize encounters between reactants on a microsecond time scale. The authors showcase the device by achieving bimolecular carbon-carbon coupling before one of the reagents can undergo a Fries rearrangement that would shift a neighboring group to the coupling site.

Visualizing a response to light

Valda Vinson

Many biological processes depend on detecting and responding to light. The response is often mediated by a structural change in a protein that begins when absorption of a photon causes isomerization of a chromophore bound to the protein. Pande et al. used x-ray pulses emitted by a free electron laser source to conduct time-resolved serial femtosecond crystallography in the time range of 100 fs to 3 ms. This allowed for the real-time tracking of the trans-cis isomerization of the chromophore in photoactive yellow protein and the associated structural changes in the protein.

Too much cleaning up

Pamela J. Hines

The complement system and microglia seek out and destroy unwanted cellular debris for the peripheral immune system as well as excess synapses in the developing brain. Hong et al. now show how the system may go haywire in adults early in the progression toward Alzheimer's disease (AD). Aberrant synapse loss is an early feature of Alzheimer's and correlates with cognitive decline. In mice susceptible to AD, complement was associated with synapses, and microglial function was required for synapse loss. The authors speculate that aberrant activation of this “trash disposal” system underlies AD pathology.

An isotope record of magnetic bacteria

Nicholas S. Wigginton

Microorganisms have shaped Earth's oceans and atmosphere over billions of years. Ancient microbes left very little direct morphological evidence of their existence in the rock record, thereby requiring geochemical clues for evidence of their activity. Amor et al. show that magnetotactic bacteria impart a distinct isotopic signature to their internal iron nanoparticles. Cultures of a modern magnetic bacterium fractionated 57Fe isotopes independent of their mass, in contrast to fractionation patterns often observed for other isotopes. Because this signature is not produced abiotically or by other iron-metabolizing bacteria, it could serve as a reliable biomarker of this ancient magnetic microbial lifestyle.

Building with designed proteins

Valda Vinson

General design principles for protein interaction specificity are challenging to extract. DNA nanotechnology, on the other hand, has harnessed the limited set of hydrogen-bonding interactions from Watson-Crick base-pairing to design and build a wide range of shapes. Protein-based materials have the potential for even greater geometric and chemical diversity, including additional functionality. Boyken et al. designed a class of protein oligomers that have interaction specificity determined by modular arrays of extensive hydrogen bond networks (see the Perspective by Netzer and Fleishman). They use the approach, which could one day become programmable, to build novel topologies with two concentric rings of helices.

Identity elements limit tRNA evolution

Philip Yeagle

A great mystery in the structure of the genetic code is the limitation on the number of unique transfer RNA (tRNA) molecules. Specifically, why are there only 20 amino acids, when 64 codon triplets can be formed from the four different nucleotide bases in DNA? Saint-Léger et al. determined that the molecular basis for this limitation derives from the restrictions imposed by the identity elements critical for binding tRNA to tRNA-modifying enzymes. The ability to expand the genetic code is therefore inhibited by the number of functional tRNA identity elements.

Sci. Adv.2, 10.1126.sciadv.1501860 (2016).

Geophysics

Applying pressure to plate tectonics

Brent Grocholski

The full range of deformation behavior of subduction zone faults that are responsible for great earthquakes and tsunamis is now clearer. Wallace et al. observed the heave of the ocean floor near the Hikurangi trench, off the east coast of New Zealand, with a network of absolute pressure gauges (see the Perspective by Tréhu). The gauges sit on the ocean floor and detect changes in pressure generated from slow-slip deformation events. Detailed geodetic observation of deformation events will finally clarify the role that such aseismic events play at major plate boundaries.